The structural landscape of Microprocessor Mediated pri-let-7 miRNAs processing.

miRNA biogenesis is initiated upon cleavage of a primary miRNA (pri-miRNA) hairpin by Microprocessor (MP), composed of the Drosha RNase III enzyme and its partner DGCR8. Multiple pri-miRNA sequence motifs affect MP recognition, fidelity, and efficiency. Here, we performed cryo-EM and biochemical studies of several let-7 family pri-miRNAs in complex with human MP. We show that MP has structural plasticity to accommodate different pri-miRNAs. These also revealed key structural features of the 5' UG sequence motif, more comprehensively represented as the "fUN" motif. Our analysis explains how the bulged nucleotide in class-II pri-let-7 members alters Drosha cleavage, generating a noncanonical precursor with 1-nt 3' overhang. Finally, the MP-SRSF3-pri-let-7f1 structure reveals how SRSF3 interacts with the CNNC motif and Drosha's PAZ-like domain, to promote proper Drosha loading onto the basal hairpin junction. Overall, our work illuminates the mechanisms for flexible recognition, accurate cleavage, and regulated processing of different pri-miRNAs by MP.

External Rotation Strength After TSA in Osteoarthritic Shoulders with Eccentric Deformity Is Not Impacted by Posterior Rotator Cuff Deficiency.

Background: Patients with persistent glenohumeral osteoarthritis symptoms despite nonoperative management may pursue anatomic total shoulder arthroplasty (TSA). TSA revision rates are higher in patients with preoperative eccentric (asymmetric posterior erosion) compared with concentric (symmetric) glenoid deformity. If posterior rotator cuff deficiency demonstrated preoperatively in patients with eccentric deformity persists after TSA, it may manifest as relative weakness in external compared with internal rotation secondary to deficient activity of the shoulder external rotator muscles. Persistent posterior rotator cuff deficiency is hypothesized to contribute to TSA failures. However, it remains unknown whether rotational strength is impaired after TSA in patients with eccentric deformity. Our goal was to determine if patients with eccentric deformity exhibit relative external rotation weakness that may be explained by posterior rotator cuff deficiency after TSA. Methods: Patients who were >1 year after TSA for primary glenohumeral osteoarthritis and had had preoperative eccentric or concentric deformity were prospectively recruited. Torque was measured and electromyography was performed during maximal isometric contractions in 26 three-dimensional direction combinations. Relative strength in opposing directions (strength balance) and muscle activity of 6 shoulder rotators were compared between groups. Results: The internal (+) and external (-) rotation component of strength balance did not differ in patients with eccentric (mean internal-external rotation component of strength balance: -7.6% ± 7.4%) compared with concentric deformity (-10.3% ± 6.8%) (mean difference: 2.7% [95% confidence interval (CI), -1.3% to 6.7%]; p = 0.59), suggesting no relative external rotation weakness. Infraspinatus activity was reduced in patients with eccentric (43.9% ± 10.4% of maximum voluntary contraction [MVC]) compared with concentric (51.3% ± 10.4% of MVC) deformity (mean difference: -7.4% [95% CI, -13.4% to -1.4%] of MVC; p = 0.04). Conclusions: A relative external rotation strength deficit following TSA was not found, despite evidence of reduced infraspinatus activity, in the eccentric-deformity group. Reduced infraspinatus activity suggests that posterior rotator cuff deficiencies may persist following TSA in patients with eccentric deformities. Longitudinal study is necessary to evaluate muscle imbalance as a contributor to higher TSA failure rates. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Safety outcomes and improvement in pain scores after radiologist-performed fluoroscopy-guided interlaminar cervical epidural steroid injection.

INTRODUCTION: Image-guided spine injections are an important tool in the management of patients with a variety of spinal pathologies. Our practice offers radiologist-performed fluoroscopy-guided interlaminar cervical epidural steroid injection (ESI) routinely performed in the outpatient setting. The purpose of this study was to evaluate clinical outcomes and improvement in pain scores after radiologist-performed cervical ESI. METHODS: An institutional database was used to retrospectively identify cervical injections performed between October 2016 and October 2022. All injections were performed at the C7-T1 level utilizing 1.0 mL of 10 mg/mL dexamethasone without epidural anesthetic. The Numerical Rating Scale (NRS) was used to assess pain improvement. Cervical MRI was reviewed to assess pre-injection cervical disease severity. Patient charts were reviewed for any post-injection complications. RESULTS: A total of 251 cervical injections in 186 patients met our inclusion criteria with mean clinical follow up of 28.5 months (range 0.2 - 73.0 months). No patients experienced any major complications after injection. Post-injection pain scores were available for 218 of 251 injections (86.9%) with mean follow-up of 11.8 days (range 6 - 57 days). There was a significant improvement in pain scores from a mean pre-injection NRS score of 5.2/10 to 3.0/10 (p < .0001). 117 patients (53.7%) reported ≥ 50% improvement after injection. Patients who had prior injection were more likely to report ≥ 50% pain improvement after subsequent injection (p = .012). CONCLUSION: Radiologist-performed fluoroscopy-guided interlaminar cervical ESI at the C7-T1 level is a safe and effective tool in the management of patients with cervical pathology.

Acceptability and feasibility of assisted telepsychiatry in routine healthcare settings in India: a qualitative study.

Technology-enabled interventions are often recommended to overcome geographical barriers to access and inequitable distribution of mental healthcare workers. The aim of this study was to examine the acceptability and feasibility of an assisted telepsychiatry model implemented in primary care settings in India. In-depth interviews were conducted with patients who received telepsychiatry consultations. Data were collected about domains such as experience with communicating with psychiatrists over a video call and feasibility of accessing services. Data were analysed using a thematic analysis approach. Patients recognized that technology enabled them to access treatment and appreciated its contribution to the improvement in their mental health condition. They reported that the telepsychiatry experience was comparable to face-to-face consultations. They had a positive experience of facilitation by counsellors and found treatment delivery in primary care non-stigmatizing. While some adapted easily to the technology platform because of increased access to technology in their daily lives, others struggled to communicate over a screen. For some, availability of care closer to their homes was convenient; for others, even the little travel involved posed a financial burden. In some cases, the internet connectivity was poor and interfered with the video calls. Patients believed that scale could be achieved through adoption of this model by the public sector, collaboration with civil society, enhanced demand generation strategies and leveraging platforms beyond health systems. Assisted telepsychiatry integrated in routine healthcare settings has the potential to make scarce specialist mental health services accessible in low resource settings by overcoming geographical and logistical barriers.

Interventions to increase help-seeking for mental health care in low- and middle-income countries: A systematic review.

Mental health problems are a significant and growing cause of morbidity worldwide. Despite the availability of evidence-based interventions, most people experiencing mental health problems remain untreated. This treatment gap is particularly large in low- and middle-income countries (LMIC) and is due to both supply-side and demand-side barriers. The aim of this systematic review is to identify and synthesise the evidence on interventions to improve help-seeking for mental health problems in LMICs. The protocol was registered a priori (Registration number: CRD42021255635). We searched eight databases using terms based on three concepts: 'mental health/illness' AND 'help-seeking' AND 'LMICs'; and included all age groups and mental health problems. Forty-two papers were eligible and included in this review. Intervention components were grouped into three categories following the steps in the help-seeking process: (1) raising mental health awareness among the general population (e.g., distribution of printed or audio-visual materials), (2) identification of individuals experiencing mental health problems (e.g., community-level screening or detection), and (3) promoting help-seeking among people in need of mental health care (e.g., sending reminders). The majority of interventions (80%) included components in a combination of the aforementioned categories. Most studies report positive outcomes, yet results on the effectiveness is mixed, with a clear trend in favour of interventions with components from more than one category. Ten out of 42 studies (24%) yielded a statistically significant effect of the intervention on help-seeking; and all targeted a combination of the aforementioned categories (i.e., raising awareness, identification and help-seeking promotion). Only six studies (14%) focused on children and adolescents. Due to the limited number of robust studies done in LMICs and the heterogeneity of study designs, outcomes and components used, no definite conclusions can be drawn with regards to the effects of individual strategies or content of the interventions.

Impact of emergency department arrival time on door-to-needle time in patients with acute stroke.

Background: This study aimed to identify which emergency department (ED) factors impact door-to-needle (DTN) time in acute stroke patients eligible for intravenous thrombolysis. The purpose of analyzing emergency department factors is to determine whether any modifiable factors could shorten the time to thrombolytics, thereby increasing the odds of improved clinical outcomes. Methods: This was a prospective observational quality registry study that included all patients that received alteplase for stroke. These data are our hospital data from the national Get With The Guidelines Registry. The Get With The Guidelines® Stroke Registry is a hospital-based program focused on improving care for patients diagnosed with a stroke. The program has over five million patients, and hospitals can access their own program data. The registry promotes the use of and adherence to scientific treatment guidelines to improve patient outcomes. The time of patient arrival to the ED was captured via the timestamp in the electronic health record. Arriving between Friday 6 p.m. and Monday 6 a.m. was classified as "weekend," regardless of the time of arrival. Time to CT, time-to-lab, and presence of a dedicated stroke team were also recorded. Emergency medical services (EMS) run sheets were used to verify arrival via ambulance. Results: Forty-nine percent of the cohort presented during the day shift, 24% during the night shift, and 27% on the weekend. A total of 85% were brought by EMS, and 15% of patients were walk-ins. The median DTN time during the day shift was 37 min (IQR 26-51, range 10-117). The median DTN time during the night shift was 59 min (IQR 39-89, range 34-195). When a dedicated stroke team was present, the median DTN time was 36 min, compared to 51 min when they were not present. The median door-to-CT time was 24 min (IQR 18-31 min). On univariate analyses, arriving during the night shift (P < 0.0001), arriving as a walk-in (P = 0.0080), and longer time-to-CT (P < 0.0001) were all associated with longer DTN time. Conversely, the presence of a dedicated stroke team was associated with a significantly shorter DTN time (P < 0.0001). Conclusion: Factors that contribute most to a delay in DTN time include arrival during the night shift, lack of a dedicated stroke team, longer time-to-CT read, and arrival as a walk-in. All of these are addressable factors from an operational standpoint and should be considered when performing quality improvement of hospital protocols.

Oxygen toxicity causes cyclic damage by destabilizing specific Fe-S cluster-containing protein complexes.

Oxygen is toxic across all three domains of life. Yet, the underlying molecular mechanisms remain largely unknown. Here, we systematically investigate the major cellular pathways affected by excess molecular oxygen. We find that hyperoxia destabilizes a specific subset of Fe-S cluster (ISC)-containing proteins, resulting in impaired diphthamide synthesis, purine metabolism, nucleotide excision repair, and electron transport chain (ETC) function. Our findings translate to primary human lung cells and a mouse model of pulmonary oxygen toxicity. We demonstrate that the ETC is the most vulnerable to damage, resulting in decreased mitochondrial oxygen consumption. This leads to further tissue hyperoxia and cyclic damage of the additional ISC-containing pathways. In support of this model, primary ETC dysfunction in the Ndufs4 KO mouse model causes lung tissue hyperoxia and dramatically increases sensitivity to hyperoxia-mediated ISC damage. This work has important implications for hyperoxia pathologies, including bronchopulmonary dysplasia, ischemia-reperfusion injury, aging, and mitochondrial disorders.

Resident Perspective of the Virtual Diagnostic Radiology Residency Interview Process: A National Survey From the Association of Program Directors in Radiology.

RATIONALE AND OBJECTIVES: The purpose of this study was to assess differences in first-year radiology resident perception of the match process and early satisfaction with residency programs between those who matched in 2020 versus 2021, the first virtual application cycle after the start of the COVID-19 pandemic. MATERIALS AND METHODS: A 33-question survey was distributed to first-year diagnostic radiology residents at programs throughout the United States through the Association of Program Directors in Radiology. Responses were collected in June of 2022 from residents who matched in 2020 and in July of 2022 from residents who matched in 2021. Questions were designed to assess applicant demographics, outcomes and attitudes towards the interview process. Comparison was made between the two cohorts. RESULTS: Of the 2231 matched residents in the 2020 and 2021 match years, 108 residents (4.8%) received, responded, and met inclusion criteria for the survey. Forty-three of 46 (92.5%) respondents that matched in 2020 interviewed in-person compared to one of 60 (1.7%) that matched in 2021 (p < 0.0001). There was no difference in satisfaction of match results, current training programs, work culture, satisfaction with facilities, and depiction of residency structure. Applicants from the 2021 cohort were more likely to express concerns about interview hoarding, having enough time to ask questions on interview days, and ability to accurately present themselves in interviews but were more likely to favor virtual interviews for future cycles. CONCLUSION: The virtual interview process is perceived neutrally or positively by most early diagnostic radiology residents and produced similar satisfactory results compared to applicants that interviewed in person. Attention should be given to concerns of those who matched virtually if the virtual interview process is to be continued.

Sural nerve: imaging anatomy and pathology.

High resolution ultrasound (US) and magnetic resonance (MR) neurography are both imaging modalities that are commonly used for assessing peripheral nerves including the sural nerve (SN). The SN is a cutaneous sensory nerve which innervates the lateral ankle and foot to the base of the fifth metatarsal. It is formed by contributing nerves from the tibial and common peroneal nerves with six patterns and multiple subtypes described in literature. In addition to the SN being a cutaneous sensory nerve, the superficial location enables the nerve to be easily biopsied and harvested for a nerve graft, as well as increasing the susceptibility to traumatic injury. As with any peripheral nerves, pathologies such as peripheral nerve sheath tumors and neuropathies can also affect the SN. By utilizing a high frequency probe in US and high-resolution MR neurography, the SN can be easily identified even with the multiple variations given the standard distal course. US and MRI are also useful in determining pathology of the SN given the specific image findings that are seen with peripheral nerves. In this review, we evaluate the normal imaging anatomy of the SN and discuss common pathologies identified on imaging.

Common strategies in empirically supported psychological interventions for alcohol use disorders: A meta-review.

ISSUES: Despite the large number of effective psychological interventions for alcohol use disorders (AUD), there is still a lack of clarity concerning the strategies that make these interventions effective. APPROACH: The overall goal of this review was to identify, examine and synthesise the information about common strategies from evidence-based psychological interventions for AUDs by conducting a review of systematic reviews, that is, a meta-review. We isolated the relevant primary studies from eligible systematic reviews and extracted information about the interventions from these studies to understand the strategies used. Analysis was restricted to narrative summaries. KEY FINDINGS: Thirteen reviews were eligible for inclusion in our meta-review. Of these, eight demonstrated the effectiveness of a range of psychological interventions-behavioural couples therapy, cognitive behaviour therapy combined with motivational interviewing, brief interventions, contingency management, psychotherapy plus brief interventions, Alcoholics Anonymous and 12-step treatment programs, family-therapy or family-involved treatment, and community reinforcement approach. The most commonly used component strategies in effective interventions for AUDs included assessment, personalised feedback, motivational interviewing, goal setting, setting and review of homework, problem solving skills and relapse prevention/management. IMPLICATIONS: Evidence about commonly used strategies in evidence-based psychological interventions for AUDs offer the possibility of creating menu-driven interventions that can be tailored to respond to individual client needs and preferences in different contexts.

Pulmonary function in cured pulmonary tuberculosis cases.

BACKGROUND: In clinical practice it has been observed that several patients of cured pulmonary tuberculosis (PTB) suffer with lung dysfunction and these problems are less documented routinely. Prevalence of these abnormalities remains unknown. Aim of this study is to estimate the lung function abnormality and exercise capacity including diffusion capacity of lung for carbon monoxide (DLCO) in cured PTB cases. METHODS: A hospital based observational descriptive study was carried out among 100 patients with PTB, who had been declared cured. These patients were evaluated by spirometry and DLCO to assess their lung function and were classified as normal or abnormal. Modified medical research council (mMRC) dyspnea scale for symptom assessment and 6-minute walk test (6MWT) to determine the exercise capacity was also done. Borg's scale was used for dyspnea assessment in 6MWT. RESULTS: 83 (83%) patients having abnormal spirometry, 17 (17%) had obstructive pattern, 32 (32%) had restrictive pattern and 34 (34%) had mixed pattern. 22 (22%) patients had mild decrease in DLCO, 43 (43%) patients had moderate decrease in DLCO, while only 4 (4%) had severe decrease in DLCO. More than half of the patients having normal spirometry had reduced in DLCO. CONCLUSION: The prevalence of abnormal lung functions is high even after complete anti-tubercular treatment. DLCO could be a better tool for evaluation of lung function in these patients. There is need to strengthen the National Programme to detect and treat TB patient earlier, also there is need to formulate guidelines for pulmonary rehabilitation of cured PTB patient.

The adverse effects of solid biomass fuel exposure on lung functions in non-smoking female population.

Background: Though, smoking is the leading cause of chronic obstructive pulmonary disease worldwide, the household air pollution due to use of solid biomass fuel is considered as a major risk factor for the development of obstructive lung disease. The aim of the study was to assess the effect of solid biomass fuel exposure on lung functions in non-smoking female population. Methods: A hospital based, descriptive cross sectional study was carried out among 140 non-smoking female patients aged 40 or more and who had been exposed to solid biomass fuel. These patients underwent spirometry to assess their lung function and were classified as obstructive, restrictive or mixed. Modified medical research council (mMRC) dyspnoea scale for symptom assessment, 6-minute walk test (6 MWT) to determine the exercise capacity and Cumulative exposure index to assess the duration of exposure were also done. Results: All 140 (100%) patients having abnormal lung function, 4 (2.86%) had restrictive pattern, 5 (3.57%) had mixed pattern and 131 (93.57%) had obstructive pattern. Of 131 patients having obstructive pattern, 11 had mild obstruction, 49 had moderate obstruction, 39 had severe obstruction and 32 had very severe obstruction. Most commonly used biomass fuel was wood (43.57%). All the patients had shortness of breath, whereas cough was present in only 35.71% cases. 77 (55%) patients presented with a dyspnoea of mMRC grade 3 and above. Conclusion: Cumulative exposure index for solid biomass fuel is directly proportional to the severity of lung impairment as well as the symptom severity.

Association of family history of cardiometabolic diseases (CMDs) and individual health behaviours: Analysis of CARRS study from South Asia.

OBJECTIVES: Family history is considered as an important predictor of cardiovascular diseases (CVDs) and diabetes. Available research findings suggest that family history of chronic diseases is associated with perceived risk of disease and adoption of healthy behaviours. We examined the association between family history of cardio-metabolic diseases (CMDs) and healthy behaviours among adults without self-reported CMDs. METHODS: Cross-sectional data of 12,484 adults, without self-reported CMDs, from the baseline survey of Centre for cArdiometabolic Risk Reduction in South-Asia (CARRS) cohort study were analysed. RESULTS: Family history was positively associated with non-smoking and high fruits & vegetables consumption in the age group of 45-64 years and moderate to high physical activity in the age group ≥65 years after adjusting for sex, education, wealth index, city and body mass index. CONCLUSIONS: Understanding perceived risks and cultural or psychological factors related to family history through ethnographic studies may deepen understanding of these associations.

E3 ubiquitin ligase FBXW7 balances airway cell fates.

The airway epithelium is composed of multiple cell types each with designated roles. A stereotyped ratio of these cells is essential for proper airway function. Imbalance of airway cell types underlies many lung diseases, including chronic obstructive pulmonary disease (COPD) and asthma. While a number of signals and transcription factors have been implicated in airway cell specification, how cell numbers are coordinated, especially at the protein level is poorly understood. Here we show that in the mouse trachea which contain epithelial cell types similar to human airway, epithelium-specific inactivation of Fbxw7, which encodes an E3 ubiquitin ligase, led to reduced club and ciliated cells, increased goblet cells, and ectopic P63-negative, Keratin5-positive transitory basal cells in the luminal layer. The protein levels of FBXW7 targets including NOTCH1, KLF5 and TGIF were increased. Inactivation of either Notch1, Klf5 but not Tgif genes in the mutant background led to attenuation of selected aspects of the phenotypes, suggesting that FBXW7 acts through different targets to control different cell fates. These findings demonstrate that protein-level regulation by the ubiquitin proteasome system is critical for balancing airway cell fates.

Essential medicines for cardiovascular diseases in India: Rapid appraisal of policies and processes at the subnational level.

Background The burden of cardiovascular diseases (CVDs) and response to health systems vary widely at the subnational level in India. Our study aimed to assess the variation in state-level access to medicines for CVDs by comparing the essential medicines lists (EMLs) at the national and subnational levels in India and by rapid appraisal of the existing policies and processes of drug procurement. Methods We assessed the inclusion of six classes of medicines for CVDs in the recent and publicly available national and subnational EMLs from July to September 2018 in the states of Telangana and Madhya Pradesh. We examined the drug procurement and distribution policies and processes using documentary review and five key informant interviews between March and June 2018. Results The WHO's EML, India's national EML, and 21 of 28 publicly available (75%) Indian state and Union Territory EMLs included all six classes of essential medicines for CVDs. However, some medicines were not included in the policy packages of essential medicines meant for primary health centres. Both the states used centralized tendering and decentralized distribution as part of the public sector drug procurement process. The requirement was based on the previous year's consumption. The approximate time between procurement planning and distribution was 7-8 months in both the states. Conclusion Substantial variation exists in the selection of drugs for CVDs in EMLs at the subnational level in India. Improving forecasting techniques for requirement of medicines and reducing time lags between forecasting and distribution to health facilities may allow for better access to essential medicines.

Integrating assisted tele-psychiatry into primary healthcare in Goa, India: a feasibility study.

Background: Tele-psychiatry is an increasingly acceptable and feasible platform to deliver mental health care with the potential to increase access to care in low-resource settings. We aim to examine the acceptability and preliminary impact of the delivery of assisted tele-psychiatry services in primary healthcare settings in Goa, India. Methods: Before-after uncontrolled treatment cohort study. In total, 161 adults with either a mental or alcohol use disorder were provided tele-consultation by psychiatrists through a customised video conferencing platform, along with medication or counselling (via trained lay counsellors) or both as needed. Data on socio-demographics, clinical outcomes and process indicators were collected at baseline and 3 months post-baseline. Paired t tests were used to assess clinical outcomes pre- and post-treatment using the General Health Questionnaire-12 (GHQ-12) and World Health Organisation Disability Adjustment Schedule (WHODAS) 2.0, and logistic regression was used to find associations between changes in these scores and various factors. Results: The most common diagnosis was depression (35%). Post-treatment, there was a significant reduction in both GHQ-12 and WHODAS 2.0 scores. Participants showed high satisfaction with the tele-psychiatry services and technology platform. Improvement in GHQ-12 score was associated with being employed [OR 8.74 (1.92-39.75, p = 0.005)] and being a homemaker [OR 6.42 (CI 1.61-25.57, p = 0.008)]. Conclusion: Treatment of mental disorders through a tele-psychiatry platform appears to be highly acceptable and is associated with improved clinical outcomes. Considering its potential for scalability, a model of assisted tele-psychiatry integrated into primary care can be an important strategy to increase access to mental healthcare in low-resource settings.

Alcohol use among adolescents in India: a systematic review.

Background: Alcohol use is typically established during adolescence and initiation of use at a young age poses risks for short- and long-term health and social outcomes. However, there is limited understanding of the onset, progression and impact of alcohol use among adolescents in India. The aim of this review is to synthesise the evidence about prevalence, patterns and correlates of alcohol use and alcohol use disorders in adolescents from India. Methods: Systematic review was conducted using relevant online databases, grey literature and unpublished data/outcomes from subject experts. Inclusion and exclusion criteria were developed and applied to screening rounds. Titles and abstracts were screened by two independent reviewers for eligibility, and then full texts were assessed for inclusion. Narrative synthesis of the eligible studies was conducted. Results: Fifty-five peer-reviewed papers and one report were eligible for inclusion in this review. Prevalence of ever or lifetime alcohol consumption ranged from 3.9% to 69.8%; and prevalence of alcohol consumption at least once in the past year ranged from 10.6% to 32.9%. The mean age for initiation of drinking ranged from 14.4 to 18.3 years. Some correlates associated with alcohol consumption included being male, older age, academic difficulties, parental use of alcohol or tobacco, non-contact sexual abuse and perpetuation of violence. Conclusion: The evidence base for alcohol use among adolescents in India needs a deeper exploration. Despite gaps in the evidence base, this synthesis provides a reasonable understanding of alcohol use among adolescents in India and can provide direction to policymakers.

Video-augmentation of the informed consent process in mental health research: An exploratory study from India.

Only around 50-75% of individuals fully understand the various aspects of informed consent in research. The aim of our study was to examine whether supplementing the conventional paper-based informed consent process with an audiovisual aid improves participants' understanding of the informed consent process and the information conveyed to them. Participants from two mental health/substance use intervention development studies were recruited for this study through consecutive sampling. They were then administered the traditional paper information and consenting process by itself or in combination with a video depicting the procedures of the study. Subsequently a bespoke questionnaire was administered to assess the participants' understanding of the information conveyed to them about the parent study. The various domains of the questionnaire were compared between those who were administered the two different consenting processes using the chi square test. 27 (58.7%) participants were administered the traditional consenting process and 19 were administered the video-supplemented consenting process. The video-supplemented consenting process was not superior to the traditional paper-based informed consent process on any of the domains examined. In settings with participants having a limited education, and in research involving people with mental health or substance use problems, further research is necessary to identify contextually relevant best practices for the informed consent process.

Magnetic resonance neurography findings in three critically ill COVID-19 patients with new onset of extremity peripheral neuropathy.

PURPOSE: Coronavirus-19 (COVID-19) is most commonly associated with respiratory syndromes, although patients are presenting more frequently with neurological symptoms. When they occur, neurological conditions most commonly involve the central nervous system, and peripheral nervous system effects, particularly in the extremities, have been less commonly described. The mechanisms of peripheral neuropathy in critically ill patients with COVID-19 are likely to be multifactorial, and extremity peripheral nerve imaging in these cases has not been well described. CASE PRESENTATION: In this case series, we describe the magnetic resonance neurography (MRN) findings in 3 critically ill patients who presented with new onset of peripheral neuropathies in the extremities, and we discuss possible common mechanisms of nerve injury, including the role of position-related nerve injury. CONCLUSIONS: MRN can be useful in identifying and localizing peripheral nerve abnormalities in the extremities of COVID-19 patients, and patients who are placed in the prone position during ventilation may be more susceptible to these injuries.

PIN and CCCH Zn-finger domains coordinate RNA targeting in ZC3H12 family endoribonucleases.

The CCCH-type zinc finger (ZnF) containing ZC3H12 ribonucleases are crucial in post-transcriptional immune homoeostasis with ZC3H12A being the only structurally studied member of the family. In this study, we present a structural-biochemical characterization of ZC3H12C, which is linked with chronic immune disorders like psoriasis. We established that the RNA substrate is cooperatively recognized by the PIN and ZnF domains of ZC3H12C and analyzed the crystal structure of ZC3H12C bound to a single-stranded RNA substrate. The RNA engages in hydrogen-bonded contacts and stacking interactions with the PIN and ZnF domains simultaneously. The ZC3H12 ZnF shows unprecedented structural features not previously observed in any member of the CCCH-ZnF family and utilizes stacking interactions via a unique combination of spatially conserved aromatic residues to align the target transcript in a bent conformation onto the ZnF scaffold. Further comparative structural analysis of ZC3H12 CCCH-ZnF suggests that a trinucleotide sequence is recognized by ZC3H12 ZnF in target RNA. Our work not only describes the initial structure-biochemical study on ZC3H12C, but also provides the first molecular insight into RNA recognition by a ZC3H12 family member. Finally, our work points to an evolutionary code for RNA recognition adopted by CCCH-type ZnF proteins.